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Liver organ-on-chip models for toxicity studies and risk assessment
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Edité par CCSD ; Royal Society of Chemistry -
International audience. The liver is a key organ that plays a pivotal role in metabolism and ensures a variety of functions in thebody, including homeostasis, synthesis of essential components, nutrient storage, and detoxification. As thecentre of metabolism for exogenous molecules, the liver is continuously exposed to a wide range ofcompounds, such as drugs, pesticides, and environmental pollutants. Most of these compounds can causehepatotoxicity and lead to severe and irreversible liver damage. To study the effects of chemicals and drugson the liver, most commonly, animal models or in vitro 2D cell cultures are used. However, data obtainedfrom animal models lose their relevance when extrapolated to the human metabolic situation and poseethical concerns, while 2D static cultures are poorly predictive of human in vivo metabolism and toxicity.As a result, there is a widespread need to develop relevant in vitro liver models for toxicology studies. Inrecent years, progress in tissue engineering, biomaterials, microfabrication, and cell biology has createdopportunities for more relevant in vitro models for toxicology studies. Of these models, the liver organ-onchip(OoC) has shown promising results by reproducing the in vivo behaviour of the cell/organ or a groupof organs, the controlled physiological micro-environment, and in vivo cellular metabolic responses. In thisreview, we discuss the development of liver organ-on-chip technology and its use in toxicity studies. First,we introduce the physiology of the liver and summarize the traditional experimental models for toxicitystudies. We then present liver OoC technology, including the general concept, materials used, cell sources,and different approaches. We review the prominent liver OoC and multi-OoC integrating the liver for drugand chemical toxicity studies. Finally, we conclude with the future challenges and directions for developingor improving liver OoC models.
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